Drug Interaction Report

GENERALLY AVOID: Coadministration with aluminum- and magnesium-containing antacids has been shown to reduce the oral bioavailability of raltegravir. The proposed mechanism is chelation of raltegravir by polyvalent cations, but changes in solubility and lipophilicity of raltegravir related to pH increases may also contribute. In drug interaction studies, raltegravir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) decreased by 44%, 49% and 63%, respectively, when a single 20 mL dose of aluminum and magnesium hydroxide antacid was administered simultaneously with raltegravir (400 mg twice daily). The Cmax, AUC and Cmin of raltegravir decreased by 51%, 51% and 56%, respectively, when the antacid was given 2 hours before raltegravir, and by 22%, 30% and 57%, respectively, when the antacid was given 2 hours after raltegravir. When given 4 hours apart, raltegravir Cmax, AUC and Cmin decreased by 22%, 19% and 60% with antacid administered first, and by 30%, 32% and 62% with raltegravir administered first. Minimal changes in raltegravir Cmax and AUC were observed when administration was staggered by 6 hours; however Cmin was still diminished by approximately 50% regardless of whether antacid was administered before or after raltegravir. When given with a single dose of antacid containing calcium carbonate 3000 mg, raltegravir Cmax, AUC and Cmin decreased by 52%, 55% and 32%, respectively. These changes are not considered clinically significant by the manufacturer.

MANAGEMENT: It is not known to what extent non-antacid aluminum and magnesium salts may interact with raltegravir. Until more information is available, it may be advisable to avoid taking raltegravir with any aluminum- and/or magnesium-containing product. Antacids containing calcium carbonate should not be used with once-daily raltegravir (HD formulation), but may be used without dose adjustment for other raltegravir products.